The goal of this project is to understand the molecular basis for the normal development of the vertebrate inner ear. Our major accomplishment this year was the characterization of the gross anatomical development of the mouse inner ear in detail using a paint-filling technique. In addition, using molecular markers, we have identified the location of each presumptive sensory organ in the rudimentary mouse otocyst. This study provided us a crude fate map of the normal inner ear and allows us to decipher malformations resulting from mutations. Several knock-out mice that have malformed inner ears are currently under investigation. Furthermore, we have completed our study using retinoic acid as a perturbant agent to address the normal development of the chicken inner ear. Our approach was to test effects of retinoic acid on inner ear development directly by implanting a bead soaked with retinoic acid to the chicken otocyst in ovo. Our results showed that retinoic acid caused dose-dependent changes in inner ear development. We found that some non-sensory structures such as the semicircular canals are more sensitive to retinoic acid than their corresponding sensory components, the cristae. In addition, some sensory organs were more susceptible to retinoic acid treatment than others. More interestingly, the three semicircular canals, though morphologically similar, were differentially affected by retinoic acid treatment. This result suggests that the molecular mechanisms for patterning of each semicircular canal are different. Other ongoing projects in the laboratory include investigating the function of BMP4 in inner ear development, fate mapping of the chicken inner ear using cell tracer, and gene expression studies in both chicken and mouse inner ears.